Causal relationships between metabolic-associated fatty liver disease and iron status: Two-sample Mendelian randomization
Causal relationships between metabolic-associated fatty liver disease and iron status: Two-sample Mendelian randomization
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代谢相关脂肪肝疾病与铁状态之间的因果关系：两样本孟德尔随机化
DOI：
10.1111/liv.15455
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发表时间：
2022-10-28
影响因子：
6.7
通讯作者：
Tao, Chuanmin
中科院分区：
文献类型：
--
作者：
He, He;Liao, Shenling;Tao, Chuanmin
背景与目的铁稳态失调在代谢相关性脂肪肝的肝脏表现中起重要作用。我们调查了五种铁代谢标记物、定期补铁和MAFLD风险的因果关系。方法从开放的全基因组关联研究数据库中获取遗传概要统计数据。采用两样本双向孟德尔随机化分析方法，包括孟德尔随机化、逆方差加权、加权中位数方法和孟德尔随机化-Egger回归分析，估计铁状态与MAFLD之间的因果关系。采用Mendelian随机化-Presso异常值检验、Cochran‘s Q检验和Mendelian随机化-Egger回归分别评价异常值、异质性和多效性。结果孟德尔随机化逆方差加权结果显示，遗传预测的肝铁含量标准差增加(数据集2：优势比1.193，95%可信区间[CI]1.074-1.326，p=.001)与肝脂肪变性风险增加有关，与加权中值估计和孟德尔随机化-艾格回归一致，尽管数据集1不显著。孟德尔随机化逆方差加权分析显示，在两个数据集(数据集1：Beta=0.038，95%CI=0.014至0.062，p=0.002；数据集2：Beta=0.081，95%CI=0.025至.136，p=0.004)中，遗传预测的MAFLD与血清铁蛋白水平的升高显著相关，数据集2的加权中位数方法而不是孟德尔随机化-Egger回归观察到了类似的结果。结论本研究揭示了铁代谢状态与MAFLD之间的遗传预测因果关系。这些发现强调了通过强调肝铁水平作为危险因素和铁蛋白水平作为预后因素来改善管理MAFLD风险的指南的必要性。
Background & Aims Dysregulated iron homeostasis plays an important role in the hepatic manifestation of metabolic-associated fatty liver disease (MAFLD). We investigated the causal effects of five iron metabolism markers, regular iron supplementation and MAFLD risk. Methods Genetic summary statistics were obtained from open genome-wide association study databases. Two-sample bidirectional Mendelian randomization analysis was performed to estimate the causal effect between iron status and MAFLD, including Mendelian randomization inverse-variance weighted, weighted median methods and Mendelian randomization-Egger regression. The Mendelian randomization-PRESSO outlier test, Cochran's Q test and Mendelian randomization-Egger regression were used to assess outliers, heterogeneity and pleiotropy respectively. Results Mendelian randomization inverse-variance weighted results showed that the genetically predicted per standard deviation increase in liver iron (Data set 2: odds ratio 1.193, 95% confidence interval [CI] 1.074-1.326, p = .001) was associated with an increased MAFLD risk, consistent with the weighted median estimates and Mendelian randomization-Egger regression, although Data set 1 was not significant. Mendelian randomization inverse-variance weighted analysis showed that genetically predicted MAFLD was significantly associated with increased serum ferritin levels in both datasets (Dataset 1: beta = .038, 95% CI = .014 to .062, p = .002; Dataset 2: beta = .081, 95% CI = .025 to .136, p = .004), and a similar result was observed with the weighted median methods for Dataset 2 instead of Mendelian randomization-Egger regression. Conclusions This study uncovered genetically predicted causal associations between iron metabolism status and MAFLD. These findings underscore the need for improved guidelines for managing MAFLD risk by emphasizing hepatic iron levels as a risk factor and ferritin levels as a prognostic factor.